While dengue has been a known disease for centuries, serious researcher on the disease dates to about World War II, when Albert Sabin (famed father of the polio vaccine) did experiments with US Army recruits, actively infecting them with the virus and studying their immune response. (It's not an exceptionally lethal virus, killing only a tiny fraction of those who are infected, but still. Times have changed.) Despite the 60+ years of work, a successful vaccine remains elusive, although there are many different groups hard at work on vaccines in various stages of clinical testing. So far, the leader is the company sanofi aventis (no caps is correct, don't ask), whose Sanofi Pasteur division has its candidate vaccine in what is called Phase 3 clinical trials, the final stage before receiving governmental approvals. Their vaccine is based on a very cool concept. They've taken the Yellow Fever vaccine, called 17D, which has been around seemingly forever--it's the first true modern vaccine--and is quite safe and very well tolerated, and spliced a piece of dengue's genetic code into the YF 17D genetic code. Since Yellow Fever and dengue are closely related viruses, this is, in concept, simple to do, and the genes that are swapped are those that encode for the surface proteins, so the human immune system "sees" a virus that looks like dengue, but the vaccine still uses the 17D proteins to replicate itself. We still need to see the results of the Phase III trial but it looks very promising at this point in time.

That said, it makes perfect sense to look for other solutions to the dengue problem, and one approach has been to control the mosquito populations. Olivia Judson of the NY Times speculated about this in her blog over two years ago. The AP report this week indicates that the company Oxitec Ltd has figured out a way to genetically engineer male mosquitoes so that they are sterile. After the science of gene manipulation, the concept is simple: release enough sterile males into the environment so that they mate with females who proceed not to reproduce, and just like that your mosquito population is lowered. The AP story notes that they've released 3 million of the critters in a small area on the Cayman Islands as a pilot project. The story also goes on to quote some worry-warts who fear that the company is jumping into an ecological experiment without having considered all of the variables. The story quotes Pete Riley, the founder of GM Freeze, a British group that opposes genetic modification. "If we remove an insect like the mosquito from the ecosystem, we don't know what the impact will be," says Riley.

Count me among the worry-warts this time. "Teaching" our immune system to recognize pathogens has been a wildly successful strategy at keeping people alive and healthy for over two centuries; messing with the environment as a means to control disease has occasionally worked, but equally as often has spectacularly failed. In the 50s and 60s, there were wholescale "malaria eradication" programs in the western hemisphere where DDT and other insecticides were used in an effort to stamp out mosquito populations, and we know how that solution worked out. One point Riley makes is that a collapse of the mosquito population will have unknown effects in the food chain, and could possibly lead to some other disease being introduced by an insect predator stepping into the breach. I'm a little skeptical about this, only because Aedes aegypti populations have taken off precisely because of human development over the past 150-200 years. These critters are as domestic and reliant on civilization as we are, as we constitute their happy hunting grounds--unlike other mosquito species, who live quite placidly in the wild. That said, I do agree that you never know what's gonna happen when you do a large-scale ecological experiment, and our these kinds of projects almost always, forgive the pun, come back to bite us.

Oxitec notes that they aren't trying to bring about permanent change since the genetically sterile males can only hang around for a generation, although to me that begs the question: what's the long-run solution? Are we going to keep introducing genetically sterile males, generation after generation, to keep mosquito populations low? And how will we define "low," anyway? Leave aside the ecological implications, which has the possibility of bringing about unintended consequences (in a way that a new vaccine almost certainly doesn't), it's an incredibly costly, top-heavy solution. And the last time I checked, a huge number of the countries that really suffer from the burden of dengue don't have the kind of cash or infrastructure that would make this kind of an approach feasible. You'd get a lot more bang for your buck if you just hired people to come visit houses and identify and eliminate all areas of still water where mosquitoes lay their eggs. Do that, and watch your skeeter population drop just as much as with the fancy genetic experiment.
--br

Wednesday, November 10, 2010

Killing a bit of time earlier this evening, and I happened upon an article in Slate--don't ask me why, I'm still trying to figure that out myself--by the sportswriter Stefan Fatsis. Stefan, who parlayed his weekend warrior soccer talents into a Paper Lion-style project as a placekicker for the Denver Broncos, has been a keen commentator on NFL issues given his insider experiences. I usually hear him on NPR, but since he had an article in Slate writing about the narcissism of Brett Favre, I figured I'd take a look with a few spare minutes.

Much as I'd like to talk about Favre, what caught my eye was an assertion that Fatsis made about another NFL primadonnish narcissist, Dallas Cowboys owner Jerry Jones. For those who don't follow the sport, Jones is regarded as something of a football equivalent of Yankees former owner George Steinbrenner: megalomanical, autocratic, a man who interferes with his coaches and management because he thinks that he knows everything about everything. Fatsis describes him like this:

...the meddling owner who considers himself a businessman, promoter, player personnel expert, general manager, entrepreneur, public speaker, draft guru, and coach.

This description is couched as part of a larger point, which is the link between Jones's personality and the Cowboys' rather spectacularly bad 1-7 record so far this season. Leave aside the devastating injury to Tony Romo, the star quarterback of the team, thus utterly preventing easy wins for the past several weeks, the Cowboys were still a bad team this year, despite being picked to be a contender to play in their very own stadium for this year's Super Bowl. The question is why they're so bad. Here's Fatsis's analysis:

It is hard to pinpoint exactly how and why an NFL team falls to pieces. There are so many moving parts. But a hefty share of the blame should go to the meddling owner...That ego seeps into every nook and cranny of that organization and clogs up the machinery. The result is a 1-7 team: uninspired and looking forward to Jan. 3, the first day of the offseason.

Truth can be found in a discussion of football, and the truth is this: it's not hard, especially in an age of easily procured data, to fact-check one's arguments, yet people often seem to rely on lazy assertions as long as it fits in with the prevailing narrative. Fatsis, in writing about Jones, makes not only a specious argument, but makes one while the facts are sitting quietly like Christmas presents, eagerly waiting to be opened and used by their owners.

You see, Jerry Jones has owned the Cowboys for over twenty years...there's a very long track record to establish if his ego does indeed "clog up the machinery." And to judge by his record--or rather, his team's record--it does nothing of the sort. I googled "Cowboys record by season" and within four minutes learned that, since 1989, when Jones bought the team, the Cowboys have a record of 185-159 for a winning percentage of .538, plus three Super Bowl victories. That's not too shabby, especially from the point of view of this long-suffering Cleveland Browns fan. Take away his one true lemon season, his first (which one could argue was a perfect storm of new owner combined with the departure of a legendary coach in Tom Landry), and his record is 184-144, with an even more impressive .560 winning percentage. So if Jones's megalomania is really responsible for their failure, why have they had so many successes during his ownership?

Instead, Fatsis cherry-picks the data, musing on the awful 1-7 record of this season, completely ignoring the rest of the data set. As a result, what we get is a tale of an owner run amok, and a moral lesson about the proper role of humility: don't think you're a genius at everything--just look at what Jerry Jones did to the Cowboys! Never mind that this reasoning is totally at odds with Steinbrenner's success as an owner, nor does it explain the perennially bad showing of the LA Clippers, owned by the hands-off Donald Sterling, who appears to take little interest in his team and almost never bids high for a player's services. Indeed, one reading of Jones's stewardship could be the polar opposite of the Slate article: if you are confident in yourself and trust your judgement, provided your judgement is good, sometimes that will pay off even if you don't rely on (or even overrule!) so-called "experts." (The Cowboys' record, it should be noted, is more erratic than consistently good, as the winning percentage only gives an average of the 20+ years and is misleading. They were the best team in football in the early-mid 90s, while from 2000-2003 they were positively mediocre. So Jones isn't always right, but sometimes he appears to have been as right as one could get.)

I don't care a great deal about Jones, and I care even less for the Cowboys, but what I found singularly irritating about Fatsis's assertion is that it could easily have been checked. Why he didn't is a mystery, since he normally is an intelligent writer. What is much more disturbing is that such lazy baseless assertions are not at all confined to the trivial world of sports commentary. And the assertions that people are going to make in the next few years may--I only say "may"--have a huge impact on how we fare locally and internationally for many more years still.

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About Me

I'm a physician and an educator with a clinical focus in infectious disease. I teach the spectrum from 3rd year medical students through senior ID fellows, and try to keep everyone loose when doing so. Whether I succeed or not, you'll have to ask them.
I am interested in issues where medicine intersects with politics, as well as how medical research is portrayed by media. In some ways my views are very much at the fringe of the rest of the physician community, although in several other critical ways I’m your typical stethoscope-wielding, white-coat-wearing, reflex-hammer-tapping doc and consider myself steeped in the traditions of the brotherhood and sisterhood.